RESUMO
The compound 2,3-dimethyl-6(2-dimethylaminoethyl)6H-indolo-(2,3-b)quinoxaline (B-220) has been shown to exhibit potent antiviral activity against herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV) and cytomegalovirus (CMV). The mechanism of antiviral action of B-220 against HSV-1 has been studied; from the results it appears that B-220 binds by intercalation into the DNA helix and then disturbs steps that are vital for viral uncoating.
Assuntos
Antivirais/farmacologia , Indóis/farmacologia , Quinoxalinas/farmacologia , Simplexvirus/efeitos dos fármacos , Adsorção , Antivirais/metabolismo , Capsídeo/efeitos dos fármacos , Capsídeo/metabolismo , Linhagem Celular , Células Cultivadas , DNA Viral/efeitos dos fármacos , DNA Viral/metabolismo , Humanos , Indóis/metabolismo , Cinética , Quinoxalinas/metabolismo , Espectrofotometria , TemperaturaAssuntos
Adenoviridae/efeitos dos fármacos , Antivirais/farmacologia , Benzenossulfonatos/farmacologia , Corantes/farmacologia , Herpesviridae/efeitos dos fármacos , Naftalenossulfonatos/farmacologia , Orthomyxoviridae/efeitos dos fármacos , Infecções por Adenoviridae/tratamento farmacológico , Âmnio , Animais , Antivirais/uso terapêutico , Benzenossulfonatos/uso terapêutico , Células Cultivadas , Corantes/uso terapêutico , Túnica Conjuntiva , Embrião de Mamíferos , Herpes Simples/tratamento farmacológico , Humanos , Influenza Humana/tratamento farmacológico , Pulmão , Masculino , Camundongos , Camundongos Endogâmicos , Naftalenossulfonatos/uso terapêuticoAssuntos
Infecções por Adenoviridae/tratamento farmacológico , Antivirais/uso terapêutico , Resfriado Comum/tratamento farmacológico , Herpes Simples/tratamento farmacológico , Influenza Humana/tratamento farmacológico , gama-Globulinas/uso terapêutico , Infecções por Adenoviridae/prevenção & controle , Âmnio , Animais , Antivirais/administração & dosagem , Linhagem Celular , Resfriado Comum/prevenção & controle , Herpes Simples/prevenção & controle , Humanos , Influenza Humana/prevenção & controle , Injeções , Injeções Intraperitoneais , Masculino , Matemática , Camundongos , Rhinovirus , Fatores de Tempo , gama-Globulinas/administração & dosagemAssuntos
Herpes Simples/tratamento farmacológico , Influenza Humana/tratamento farmacológico , gama-Globulinas/administração & dosagem , Animais , Humanos , Injeções Intravenosas , Camundongos , Orthomyxoviridae/efeitos dos fármacos , Simplexvirus/efeitos dos fármacos , Fatores de Tempo , gama-Globulinas/farmacologia , gama-Globulinas/uso terapêuticoRESUMO
The antiherpesvirus activity of 14 derivatives of indoloquinoxaline was tested. The most active was 2,3-dimethyl(dimethylaminoethyl)5H-indolo-(2,3-b)quinoxaline, also called B-220. The antiherpesvirus mechanism of B-220 was sought. The compound inhibited replication of herpes simplex virus type 1, cytomegalovirus, and varicella-zoster virus in tissue culture at concentrations of 1 to 5 microM, depending on the cell type used for assay and the amount of virus. Cellular toxicity was seen at a concentration of 10 to 30 microM, and antiviral activity in the human bladder cancer and human embryonic lung fibroblast cell lines tested was found at concentrations 3 to 15 times lower than the concentrations causing cellular toxicity. Viral DNA synthesis, as well as production of early and late viral proteins, was inhibited at 0.5 to 4.5 microM B-220, but viral DNA polymerases tested in vitro were not inhibited at these concentrations. There was no interaction with the pyrophosphate analog foscarnet, and no reversal of the antiviral activity of B-220 occurred with naturally occurring nucleosides. We conclude that the antiviral effect depends on the multiplicity of infection and may occur at the level of viral DNA synthesis and that no interference occurs with pyrophosphate analogs or nucleosides. The more potent activity against viral DNA than against cellular DNA may be caused by a true selectivity for herpesvirus DNA or by the higher metabolism of viral DNA in infected cells.